Evidence for time-of-day dependent effect of neurotoxic dorsomedial hypothalamic lesions on food anticipatory circadian rhythms in rats

The dorsomedial hypothalamus (DMH) is a site of circadian clock gene and immediate early gene expression inducible by daytime restricted feeding schedules that entrain food anticipatory circadian rhythms in rats and mice. The role of the DMH in the expression of anticipatory rhythms has been evaluated using different lesion methods. Partial lesions created with the neurotoxin ibotenic acid (IBO) have been reported to attenuate food anticipatory rhythms, while complete lesions made with radiofrequency current leave anticipatory rhythms largely intact. We tested a hypothesis that the DMH and fibers of passage spared by IBO lesions play a time-of-day dependent role in the expression of food anticipatory rhythms. Rats received intra-DMH microinjections of IBO and activity and body temperature (T(b)) rhythms were recorded by telemetry during ad-lib food access, total food deprivation and scheduled feeding, with food provided for 4-h/day for 20 days in the middle of the light period and then for 20 days late in the dark period. During ad-lib food access, rats with DMH lesions exhibited a lower amplitude and mean level of light-dark entrained activity and T(b) rhythms. During the daytime feeding schedule, all rats exhibited food anticipatory activity and T(b) rhythms that persisted during 2 days without food in constant dark. In some rats with partial or total DMH ablation, the magnitude of the anticipatory rhythm was weak relative to most intact rats. When mealtime was shifted to the late night, the magnitude of the food anticipatory activity rhythms in these cases was restored to levels characteristic of intact rats. These results confirm that rats can anticipate scheduled daytime or nighttime meals without the DMH. Improved anticipation at night suggests a modulatory role for the DMH in the expression of food anticipatory activity rhythms during the daily light period, when nocturnal rodents normally sleep.     

Circadian discrimination of reward: evidence for simultaneous yet separable food- and drug-entrained rhythms in the rat

A unique extra-suprachiasmatic nucleus (SCN) oscillator, operating independently of the light-entrainable oscillator, has been hypothesized to generate feeding and drug-related rhythms. To test the validity of this hypothesis, sham-lesioned (Sham) and SCN-lesioned (SCNx) rats were housed in constant dim-red illumination (LL(red)) and received a daily cocaine injection every 24 h for 7 d (Experiment 1). In a second experiment, rats underwent 3-h daily restricted feeding (RF) followed 12 d later by the addition of daily cocaine injections given every 25 h in combination with RF until the two schedules were in antiphase. In both experiments, body temperature and total activity were monitored continuously. Results from Experiment 1 revealed that cocaine, but not saline, injections produced anticipatory increases in temperature and activity in SCNx and Sham rats. Following withdrawal from cocaine, free-running temperature rhythms persisted for 2-10 d in SCNx rats. In Experiment 2, robust anticipatory increases in temperature and activity were associated with RF and cocaine injections; however, the feeding periodicity (23.9 h) predominated over the cocaine periodicity. During drug withdrawal, the authors observed two free-running rhythms of temperature and activity that persisted for >14 d in both Sham and SCNx rats. The periods of the free-running rhythms were similar to the feeding entrainment (period = 23.7 and 24.0 h, respectively) and drug entrainment (period = 25.7 and 26.1 h, respectively). Also during withdrawal, the normally close correlation between activity and temperature was greatly disrupted in Sham and SCNx rats. Taken together, these results do not support the existence of a single oscillator mediating the rewarding properties of both food and cocaine. Rather, they suggest that these two highly rewarding behaviors can be temporally isolated, especially during drug withdrawal. Under stable dual-entrainment conditions, food reward appears to exhibit a slightly greater circadian influence than drug reward. The ability to generate free-running temperature rhythms of different frequencies following combined food and drug exposures could reflect a state of internal desynchrony that may contribute to the addiction process and drug relapse.     

Circadian clocks for all meal-times: anticipation of 2 daily meals in rats

Anticipation of a daily meal in rats has been conceptualized as a rest-activity rhythm driven by a food-entrained circadian oscillator separate from the pacemaker generating light-dark (LD) entrained rhythms. Rats can also anticipate two daily mealtimes, but whether this involves independently entrained oscillators, one 'continuously consulted' clock, cue-dependent non-circadian interval timing or a combination of processes, is unclear. Rats received two daily meals, beginning 3-h (meal 1) and 13-h (meal 2) after lights-on (LD 14:10). Anticipatory wheel running began 68±8 min prior to meal 1 and 101±9 min prior to meal 2 but neither the duration nor the variability of anticipation bout lengths exhibited the scalar property, a hallmark of interval timing. Meal omission tests in LD and constant dark (DD) did not alter the timing of either bout of anticipation, and anticipation of meal 2 was not altered by a 3-h advance of meal 1. Food anticipatory running in this 2-meal protocol thus does not exhibit properties of interval timing despite the availability of external time cues in LD. Across all days, the two bouts of anticipation were uncorrelated, a result more consistent with two independently entrained oscillators than a single consulted clock. Similar results were obtained for meals scheduled 3-h and 10-h after lights-on, and for a food-bin measure of anticipation. Most rats that showed weak or no anticipation to one or both meals exhibited elevated activity at mealtime during 1 or 2 day food deprivation tests in DD, suggesting covert operation of circadian timing in the absence of anticipatory behavior. A control experiment confirmed that daytime feeding did not shift LD-entrained rhythms, ruling out displaced nocturnal activity as an explanation for daytime activity. The results favor a multiple oscillator basis for 2-meal anticipatory rhythms and provide no evidence for involvement of cue-dependent interval timing.     

Circadian Discrimination of Reward: Evidence for Simultaneous Yet Separable Food- and Drug-Entrained Rhythms in the Rat

A unique extra-suprachiasmatic nucleus (SCN) oscillator, operating independently of the light-entrainable oscillator, has been hypothesized to generate feeding and drug-related rhythms. To test the validity of this hypothesis, sham-lesioned (Sham) and SCN-lesioned (SCNx) rats were housed in constant dim-red illumination (LL_red) and received a daily cocaine injection every 24?h for 7 d (Experiment 1). In a second experiment, rats underwent 3-h daily restricted feeding (RF) followed 12 d later by the addition of daily cocaine injections given every 25?h in combination with RF until the two schedules were in antiphase. In both experiments, body temperature and total activity were monitored continuously. Results from Experiment 1 revealed that cocaine, but not saline, injections produced anticipatory increases in temperature and activity in SCNx and Sham rats. Following withdrawal from cocaine, free-running temperature rhythms persisted for 2–10 d in SCNx rats. In Experiment 2, robust anticipatory increases in temperature and activity were associated with RF and cocaine injections; however, the feeding periodicity (23.9?h) predominated over the cocaine periodicity. During drug withdrawal, the authors observed two free-running rhythms of temperature and activity that persisted for >14 d in both Sham and SCNx rats. The periods of the free-running rhythms were similar to the feeding entrainment (period?=?23.7 and 24.0?h, respectively) and drug entrainment (period?=?25.7 and 26.1?h, respectively). Also during withdrawal, the normally close correlation between activity and temperature was greatly disrupted in Sham and SCNx rats. Taken together, these results do not support the existence of a single oscillator mediating the rewarding properties of both food and cocaine. Rather, they suggest that these two highly rewarding behaviors can be temporally isolated, especially during drug withdrawal. Under stable dual-entrainment conditions, food reward appears to exhibit a slightly greater circadian influence than drug reward. The ability to generate free-running temperature rhythms of different frequencies following combined food and drug exposures could reflect a state of internal desynchrony that may contribute to the addiction process and drug relapse. (Author correspondence: heiko@vetmed.wsu.edu)     

Dopaminergic Regulation of Circadian Food Anticipatory Activity Rhythms in the Rat

Circadian activity rhythms are jointly controlled by a master pacemaker in the hypothalamic suprachiasmatic nuclei (SCN) and by food-entrainable circadian oscillators (FEOs) located elsewhere. The SCN mediates synchrony to daily light-dark cycles, whereas FEOs generate activity rhythms synchronized with regular daily mealtimes. The location of FEOs generating food anticipation rhythms, and the pathways that entrain these FEOs, remain to be clarified. To gain insight into entrainment pathways, we developed a protocol for measuring phase shifts of anticipatory activity rhythms in response to pharmacological probes. We used this protocol to examine a role for dopamine signaling in the timing of circadian food anticipation. To generate a stable food anticipation rhythm, rats were fed 3h/day beginning 6-h after lights-on or in constant light for at least 3 weeks. Rats then received the D2 agonist quinpirole (1 mg/kg IP) alone or after pretreatment with the dopamine synthesis inhibitor α-methylparatyrosine (AMPT). By comparison with vehicle injections, quinpirole administered 1-h before lights-off (19h before mealtime) induced a phase delay of activity onset prior to the next meal. Delay shifts were larger in rats pretreated with AMPT, and smaller following quinpirole administered 4-h after lights-on. A significant shift was not observed in response to the D1 agonist SKF81297. These results provide evidence that signaling at D2 receptors is involved in phase control of FEOs responsible for circadian food anticipatory rhythms in rats.     

Food-anticipatory rhythms under 24-hour schedules of limited access to single macronutrients

Food-restricted rats anticipate a fixed daily mealtime by entrainment of a circadian timekeeping mechanism separate from that which generates daily light-entrainable activity rhythms. The entrainment pathways and rhythm-generating substrates for food-anticipatory rhythms are unknown. In this study, we attempted to define minimal food-related stimuli necessary or sufficient for food anticipation by employing schedules of restricted macronutrient availability, with or without free access to a complementary diet. Rats did not anticipate a daily meal of protein, carbohydrate, or fat, as measured by tilt-cage, running-wheel, or food-bin activity, when they had free access to other nutrients. However, rats did anticipate single-macronutrient meals when they were limited to only two, larger, complementary meals each day (protein-fat, protein-carbohydrate) providing a reduced total number of calories. Previous work has shown that caloric restriction per se is not a prerequisite for food anticipation. In combination with that study, the present results indicate that the size of a nutrient meal, in absolute terms or relative to total daily nutrient intake, is of pre-eminent importance in determining its value as a synchronizer of anticipatory rhythms. The results further suggest that physiological responses unique to the ingestion and absorption of any particular macronutrient are not necessary components of the entrainment pathway.     

Ghrelin mediates anticipation to a palatable meal in rats

Food anticipatory activity (FAA) is displayed in rats when access to food is restricted to a specific time frame of their circadian phase, a behavior thought to reflect both hunger and the motivation to eat. Rats also display FAA in a feeding schedule with ad libitum access to normal chow, but limited availability of a palatable meal, which is thought to involve mainly motivational aspects. The orexigenic hormone ghrelin has been implicated in FAA in rodents with restricted access to chow. Because ghrelin plays an important role not only in the control of food intake, but also in reward, we sought to determine the role of ghrelin in anticipation to a palatable meal. Plasma ghrelin levels of non-restricted rats that anticipated chocolate correlated positively with FAA and were increased compared with chow-fed control rats. Furthermore, centrally injected ghrelin increased, whereas an antagonist of the ghrelin receptor decreased, the anticipation to chocolate. Therefore, we hypothesize that central ghrelin signaling is able to mediate the motivational drive to eat.     

Palatable Meal Anticipation in Mice

The ability to sense time and anticipate events is a critical skill in nature. Most efforts to understand the neural and molecular mechanisms of anticipatory behavior in rodents rely on daily restricted food access, which induces a robust increase of locomotor activity in anticipation of daily meal time. Interestingly, rats also show increased activity in anticipation of a daily palatable meal even when they have an ample food supply, suggesting a role for brain reward systems in anticipatory behavior, and providing an alternate model by which to study the neurobiology of anticipation in species, such as mice, that are less well adapted to “stuff and starve” feeding schedules. To extend this model to mice, and exploit molecular genetic resources available for that species, we tested the ability of wild-type mice to anticipate a daily palatable meal. We observed that mice with free access to regular chow and limited access to highly palatable snacks of chocolate or “Fruit Crunchies” avidly consumed the snack but did not show anticipatory locomotor activity as measured by running wheels or video-based behavioral analysis. However, male mice receiving a snack of high fat chow did show increased food bin entry prior to access time and a modest increase in activity in the two hours preceding the scheduled meal. Interestingly, female mice did not show anticipation of a daily high fat meal but did show increased activity at scheduled mealtime when that meal was withdrawn. These results indicate that anticipation of a scheduled food reward in mice is behavior, diet, and gender specific.     

Enhanced Food Anticipatory Activity Associated with Enhanced Activation of Extrahypothalamic Neural Pathways in Serotonin2C Receptor Null Mutant Mice

The ability to entrain circadian rhythms to food availability is important for survival. Food-entrained circadian rhythms are characterized by increased locomotor activity in anticipation of food availability (food anticipatory activity). However, the molecular components and neural circuitry underlying the regulation of food anticipatory activity remain unclear. Here we show that serotonin_2C receptor (5-HT2CR) null mutant mice subjected to a daytime restricted feeding schedule exhibit enhanced food anticipatory activity compared to wild-type littermates, without phenotypic differences in the impact of restricted feeding on food consumption, body weight loss, or blood glucose levels. Moreover, we show that the enhanced food anticipatory activity in 5-HT2CR null mutant mice develops independent of external light cues and persists during two days of total food deprivation, indicating that food anticipatory activity in 5-HT2CR null mutant mice reflects the locomotor output of a food-entrainable oscillator. Whereas restricted feeding induces c-fos expression to a similar extent in hypothalamic nuclei of wild-type and null mutant animals, it produces enhanced expression in the nucleus accumbens and other extrahypothalamic regions of null mutant mice relative to wild-type subjects. These data suggest that 5-HT2CRs gate food anticipatory activity through mechanisms involving extrahypothalamic neural pathways.     

Anticipatory activity rhythms under daily schedules of water access in the rat.

Rats anticipate a fixed daily feeding time by entrainment of a component of their multioscillatory circadian system. The range of stimuli capable of entraining this component is little studied. Previous studies suggest that restricted water access is not an effective entrainment stimulus, as measured by general locomotion. The present study re-examined the issue, using two other measures of activity: wheel running and activity at a food-water delivery bin. Rats restricted to 1 hr of water each day in the middle of the light and to food in the 12-hr dark period showed no anticipation of this event in the wheel-running measure, but some rats did show anticipation in the delivery bin activity measure. Rats (bin activity measure only) restricted to 1 hr of water and 1 hr of food separated by intervals of 7, 10, or 12 hr, in either the light or the dark, showed consistent anticipation of food access time but little or no anticipation of water access time. Water access time also did not sustain food anticipatory rhythms in animals whose food-water schedules were reversed. However, deprivation of water or of both food and water for 72 or 90 hr was usually associated with specific increases in bin activity at both the usual feeding and drinking times. Water access, like food, appears to provide cues capable of entraining an anticipatory circadian mechanism. Differences in the type and amount of anticipatory activity preceding these events may reflect differences in the strengths of the two entrainment cues and/or in the activity levels or specific behavioral strategies promoted by hunger and thirst.     

Alterations in plasma concentrations of testosterone, LH, and prolactin associated with mating in the male rat.

The hormonal response of the male rat to sexual activity was investigated in two studies. In the first, no evidence of a chronic elevation in plasma levels of testosterone (T), LH, or prolactin (PRL) was observed in sexually experienced rats compared to naive controls. Both groups showed an acute increase in plasma levels of all three hormones following mating, but the increases shown by the experienced group were more pronounced. In the second study, plasma levels of T, LH and PRL rose in sexually experienced male rats following exposure to a mating arena whether it contained an estrous female, an anestrous female, or no other animal. However, the increases were considerably larger in the group exposed to estrous females. It is suggested that plasma hormones rise in anticipation of mating, although not to the same extent as following mating, and that the anticipatory rise may function to initiate or facilitate mating behavior.     

Voluntary exercise contributed to an amelioration of abnormal feeding behavior,locomotor activity and ghrelin production concomitantly with a weight reduction in high fat diet-induced obese rats

In the present study, effects of voluntary exercise in an obese animal model were investigated in relation to the rhythm of daily activity and ghrelin production. Male Sprague–Dawley rats were fed either a high fat diet (HFD) or a chow diet (CD) from four to 16 weeks old. They were further subdivided into either an exercise group (HFD-Ex, CD-Ex) with a running wheel for three days of every other week or sedentary group (HFD-Se, CD-Se). At 16 weeks old, marked increases in body weight and visceral fat were observed in the HFD-Se group, together with disrupted rhythms of feeding and locomotor activity. The induction of voluntary exercise brought about an effective reduction of weight and fat, and ameliorated abnormal rhythms of activity and feeding in the HFD-Ex rats. Wheel counts as voluntary exercise was greater in HFD-Ex rats than those in CD-Ex rats. The HFD-obese had exhibited a deterioration of ghrelin production, which was restored by the induction of voluntary exercise. These findings demonstrated that abnormal rhythms of feeding and locomotor activity in HFD-obese rats were restored by infrequent voluntary exercise with a concomitant amelioration of the ghrelin production and weight reduction. Because ghrelin is related to food anticipatory activity, it is plausible that ghrelin participates in the circadian rhythm of daily activity including eating behavior. A beneficial effect of voluntary exercise has now been confirmed in terms of the amelioration of the daily rhythms in eating behavior and physical activity in an animal model of obesity.     

Circadian and ultradian activity rhythms in male long‐evans rats: Relationship to feeding

Abstract

Rats exhibit ultradian as well as circadian rhythms in activity. Short‐term activity rhythms appear to result from bouts of feeding‐related behavior interspersed with periods of quiescence. We examined the relationship of activity to feeding in 12 male Long‐Evans derived rats during ad lib and restricted feeding (RF) conditions to determine the effect of RF on both circadian and ultradian activity rhythms. By the end of 20 days of RF all animals exhibited an ultradian periodicity of approximately 12 hours. A twenty‐four hour rhythm in feeding persisted, apparently due to the rats adapting to the diurnal feeding period. General findings were that RF resulted in anticipatory activity prior to feeding and that short‐term activity fluctuations and investigations of the food bin continued during RF even though overall nocturnal activity decreased. The results suggest that male rats of this strain exhibit ultradian activity rhythms that appear to be strongly related to feeding.     

Nonphotic phase shifting in female Syrian hamsters: interactions with the estrous cycle

Nonphotic phase shifting of circadian rhythms was examined in female Syrian hamsters. Animals were stimulated at zeitgeber time 4.5 by either placing them in a novel running wheel or by transferring them to a clean home cage. Placement in a clean home cage was more effective than novel wheel treatment in stimulating large (> 1.5 h) phase shifts. Peak phase shifts (ca. 3.5 h) and the percentage of females showing large phase shifts were comparable to those found in male hamsters stimulated with novel wheels. The amount of activity induced by nonphotic stimulation and the amount of phase shifting varied slightly with respect to the 4-day estrous cycle. Animals tended to run less and shift less on the day of estrus. Nonphotic stimulation on proestrus often resulted in a 1-day delay of the estrous cycle reflected in animals' postovulatory vaginal discharge and the expression of sexual receptivity (lordosis). This delay of the estrous cycle was associated with large phase advances and high activity. These results extend the generality of nonphotic phase shifting to females for the first time and raise the possibility that resetting of circadian rhythms can induce changes in the estrous cycle.     

Photic and Pineal Modulation of Food Anticipatory Circadian Activity Rhythms in Rodents

Restricted daily feeding schedules entrain circadian oscillators that generate food anticipatory activity (FAA) rhythms in nocturnal rodents. The location of food-entrainable oscillators (FEOs) necessary for FAA remains uncertain. The most common procedure for inducing circadian FAA is to limit food access to a few hours in the middle of the light period, when activity levels are normally low. Although light at night suppresses activity (negative masking) in nocturnal rodents, it does not prevent the expression of daytime FAA. Nonetheless, light could reduce the duration or magnitude of FAA. If so, then neural or genetic ablations designed to identify components of the food-entrainable circadian system could alter the expression of FAA by affecting behavioral responses to light. To assess the plausibility of light as a potential mediating variable in studies of FAA mechanisms, we quantified FAA in rats and mice alternately maintained in a standard full photoperiod (12h of light/day) and in a skeleton photoperiod (two 60 min light pulses simulating dawn and dusk). In both species, FAA was significantly and reversibly enhanced in the skeleton photoperiod compared to the full photoperiod. In a third experiment, FAA was found to be significantly attenuated in rats by pinealectomy, a procedure that has been reported to enhance some effects of light on behavioral circadian rhythms. These results indicate that procedures affecting behavioral responses to light can significantly alter the magnitude of food anticipatory rhythms in rodents.     

Effects of neonatal testosterone treatment on pacing behaviors and development of a conditioned place preference

Two experiments assessed the effects of neonatal testosterone treatment on paced mating behavior and conditioned place preference in female rats. In both experiments, females received s.c. injections of 5.0 microg testosterone propionate or oil vehicle at three days postpartum. As adults, females were ovariectomized and given s.c. injections of 10 microg estradiol benzoate and 500 microg progesterone, 48 and 4 h before mating, respectively. In Experiment 1, TP- and Oil-treated females exhibited similar high levels of lordosis responsiveness, but TP-treated females showed increased intervals between mounts and between intromissions in paced and non-paced mating conditions compared to control females. The effect was particularly pronounced during paced mating, when contact return latencies were increased approximately 2-fold by TP treatment. TP-treated females showed exaggerated pacing behavior, showing significantly greater return latencies after intromissions than Oil-treated females. In Experiment 2, TP- and Oil-treated groups were tested in a conditioned place preference paradigm to determine if the behavioral changes observed in Experiment 1 were in part a result of changes in the perceived reward produced by paced mating. TP treated and control females developed equivalent preferences for places associated with paced but not non-paced mating, indicating that neonatal TP treatment at this dosage does not disrupt or enhance the conditioned place preference induced by paced mating. The results of the two experiments demonstrate that neonatal TP treatment alters the display of pacing behavior but not the reward state induced by paced mating, and suggest that TP affects neural substrates involved in performance of paced mating without effects on those controlling lordosis or place preference conditioning.     

Enhancement and suppression of ultradian and circadian rhythms across the female hamster reproductive cycle

The impact of ovarian hormones on hamster ultradian rhythms (URs) is unknown. We concurrently monitored URs and circadian rhythms (CRs) of home cage locomotor activity during the estrous cycle, pregnancy, and lactation of Syrian hamsters. URs with a mean period of 4-5 h were evident during the dark phase in more than 90% of females on days 1 and 2 of the estrous cycle but were significantly less prevalent on cycle days 3 and 4. The period of the UR did not vary as a function of estrous cycle stage, but at all stages, the UR period was longer in the dark than the light phase. The UR acrophase occurred significantly earlier on cycle day 4 than on days 1 and 2, and UR robustness and amplitude were reduced on days 3 and 4. Robustness, mesor, and amplitude of CRs were greater during cycle days 3 and 4; timing of the CR acrophase was delayed on day 4 relative to all other cycle days. Effects of the estrous cycle on URs were evident only during the dark phase. The proportion of hamsters displaying dark phase URs increased significantly during early and late gestation and decreased during lactation. Pregnancy significantly increased UR complexity, robustness, and amplitude. The emergence of URs over gestation was paralleled by decrements in the robustness and amplitude of CRs, which also were absent in a significant proportion of dams during lactation but re-emerged at weaning of litters. The changing endocrine profile of the estrous cycle, hormonal dynamics of pregnancy and lactation, and nursing demands placed on dams are each associated with alterations in the expression of ultradian and circadian locomotor rhythms. Diminution of CRs and augmentation of URs may afford greater behavioral flexibility during life stages when interactions with mates and offspring are less predictable.     

"Feeding time" for the brain: a matter of clocks.

Circadian clocks are autonomous time-keeping mechanisms that allow living organisms to predict and adapt to environmental rhythms of light, temperature and food availability. At the molecular level, circadian clocks use clock and clock-controlled genes to generate rhythmicity and distribute temporal signals. In mammals, synchronization of the master circadian clock located in the suprachiasmatic nuclei of the hypothalamus is accomplished mainly by light stimuli. Meal time, that can be experimentally modulated by temporal restricted feeding, is a potent synchronizer for peripheral oscillators with no clear synchronizing influence on the suprachiasmatic clock. Furthermore, food-restricted animals are able to predict meal time, as revealed by anticipatory bouts of locomotor activity, body temperature and plasma corticosterone. These food anticipatory rhythms have long been thought to be under the control of a food-entrainable clock (FEC). Analysis of clock mutant mice has highlighted the relevance of some, but not all of the clock genes for food-entrainable clockwork. Mutations of Clock or Per1 do not impair expression of food anticipatory components, suggesting that these clock genes are not essential for food-entrainable oscillations. By contrast, mice mutant for Npas2 or deficient for Cry1 and Cry2 show more or less altered responses to restricted feeding conditions. Moreover, a lack of food anticipation is specifically associated with a mutation of Per2, demonstrating the critical involvement of this gene in the anticipation of meal time. The actual location of the FEC is not yet clearly defined. Nevertheless, current knowledge of the putative brain regions involved in food-entrainable oscillations is discussed. We also describe several neurochemical pathways, including orexinergic and noradrenergic, likely to participate in conveying inputs to and outputs from the FEC to control anticipatory processes.     

Effects of Pregnancy and Parturition on Free-Running Circadian Activity Rhythms in the Rat

Alterations in circadian rhythms have previously been associated with estrous and seasonal changes in reproductive state. In the present study we explored the effects of the reproductive events of pregnancy and parturition on free-running circadian activity rhythms in the rat. Free-running rhythms were monitored before mating, during pregnancy, and following parturition and removal of pups. Systematic and long-lasting alterations of the period of the free-running activity rhythm were seen following parturition. The effects of estrous, seasonal, and gestational reproductive states on circadian rhythms may be mediated by the endocrine events which accompany these states.